Thirty to 50 percent of patients diagnosed with gastroesophageal reflux disease (GERD) are not satisfied with symptom control derived from proton pump inhibitors (PPI). This group of patients; PPI non-responders (PPI- NR), pursue further diagnostic procedures and interventions with low yield. This approach is problematic because symptoms are not related to pathologic reflux in at least 50% of PPI-NRs referred for ambulatory reflux testing and therefore it does not lead to improved outcomes or even inform us as to why a patient did not respond to PPI. The development of novel therapies for this group is limited by lack of agreement on the definition of a PPI responder and the lack of a model that accounts for the heterogeneity of continued symptom generation. Our goal is to validate a PPI-NR model that accounts for factors above and beyond pathologic reflux, reducing the need for low-yield ambulatory reflux monitoring and informing the development of novel treatments. Study 1 will provide an equation in which pre-test clinical and questionnaire data sufficiently enables probability estimation for each of 4 reflux phenotypes, derived from ambulatory reflux monitoring. Study 2 will yield a similar equation which will predict one's ability to withdraw PPI therapy when indicated. PUBLIC HEALTH RELEVANCE: Gastroesophageal reflux disease (GERD) is an increasingly common medical condition affecting at least ten percent of the adult US population. Despite the fact that proton pump inhibitors (PPI) are extremely effective, up to 30-50% of patients are unsatisfied with their response and continue to have refractory symptoms. This proposal seeks to identify the reason for continued symptoms and to determine whether a systematic diagnostic protocol will better define treatment strategies for PPI non-responders.